Type 2 diabetes is associated with enormous morbidity and mortality attributable to heart disease caused by atherosclerosis in coronary arteries that supply blood to the heart muscle itself. Two processes associated with diabetes, inflammation and heightened coagulability of blood, have been implicated in accelerating the coronary disease. The NIH-sponsored BARI 2D trial, which involves more than 40 clinical sites studying 2800 patients with both type 2 diabetes and coronary artery disease being followed for 5 years, is comparing two types of therapy for diabetes one that results in increased concentrations of insulin in blood and the other in reduction of resistance to insulin in tissues. This project is designed to characterize effects of each of the two types of therapy on inflammation and procoagulation and to determine whether amelioration of either or both leads to retardation of progression of coronary disease and its sequelae. Markers of both inflammation and procoagulation (C-reactive protein, fibrinogen, D-dimer, and fibrinopeptide A) will be assayed in serially obtained blood samples. Results will be analyzed with respect to all the end points in BARI 2D including morbidity and mortality attributable to coronary artery disease. The BARI 2D trial, sponsored by the National Institutes of Health, was initiated to address two questions: 1) is invasive compared with noninvasive management advantageous or disadvantageous compared with aggressive medical management alone in patients with type 2 diabetes and overt coronary artery disease; and 2) does the mode of achieving metabolic control (insulin sensitizing compared with insulin providing regimens) influence morbidity, mortality, and the progression of coronary disease in patients with type 2 diabetes and overt coronary artery disease? The Principal Investigator (PI) of this proposal is the PI of the BARI 2D Fibrinolytic System Core Laboratory funded by the NIH through an R01 grant. We propose to study all 2800 patients in the BARI 2D trial to determine the extent to which inflammation, procoagulation, neither, or both are modified by each of the therapeutic approaches to be implemented in BARI 2D. In addition, we seek to determine whether attenuation of either or both results from treatment with an insulin sensitizing regimen and, if so, whether attenuation presages improved clinical outcomes and, therefore, implicates inflammation, procoagulation or both as a determinant of progression of coronary artery disease in type 2 diabetes.